Over the last century, the transsphenoidal approach has evolved into the first-line method of treatment for sellar as well as select groups of parasellar and suprasellar lesions. The journey to its current popularity has been marked by controversy and near abandonment in the late 1920s, followed by its renaissance in the late 1960s. Despite the profound skepticism with which this procedure was viewed, several visionary neurosurgeons persevered through its nadir in popularity, preserving this surgical corridor to the skull base. Advances in medical and surgical techniques, paralleling an improved understanding of pituitary pathophysiology, contributed to its resurgence. The transsphenoidal procedures now performed stem from an array of modifications and refinements accumulated through nearly 100 years of medical and surgical evolution. This era's critical innovations and neurosurgical personalities are the topic of this historical overview.